This project is part of a continuing program of research in our laboratories directed toward improved understanding of the molecular mechanisms and cellular functions of ion transport across cell membranes. The first objective of the experiments proposed in this project is to characterize further the molecular basis of the Na-Li countertransport system which we have recently described in human red cells. We are particularly interested in the regulation of this process by hormones and drugs. A second objective is to explore the inheritance of this Na-Li countertransport system in human red cells, and if possible, other human cells. We will study the relation between the genes which regulate the expression of this transport system and genes which may be involved in predisposing toward different forms of hypertension and certain other syndromes such as cystic fibrosis and affective disorders. A third objective is to find out whether this system is present in the membranes of other human cells such as lymphocytes and fibroblasts, and mouse neuroblastoma. If so, we will investigate its characteristics and its relations to other modes of Na transport in these cells.